MS is a frequently disabling autoimmune disease affecting approximately 350,000 people in the United States. It is among the most disabling diseases in the United States, with 81% of all patients out of the workforce. More that two decades of research has consistently shown a relationship between stressful life events (SLEs), in particular non-traumatic family and work stressors, and subsequent clinical exacerbation. Furthermore, we have shown that non-traumatic SLEs increase the risk of the subsequent appearance of new gadolinium enhancing (Gd+) magnetic resonance imaging (MRI) brain lesions, an early marker of MS inflammation and blood-brain barrier (BBB'breakdown. The purpose of this study is to determine the efficacy of cognitive behavioral therapy for MS (CBT. MS), a stress management program we have developed specifically for MS, in reducing the occurrence of new brain lesions in people with relapsing-remitting multiple sclerosis (RRMS). RRMS was selected over other types, because it is the most common form of MS and it is more likely than other types to be associated with clinical exacerbation and Gd+ MRI. One hundred and twelve patients will be enrolled for 2 years. To ensure equivalent medical treatment across patients and treatment arms, all patients will receive neurological care through the University of California, San Francisco (UCSF) MS Center. Patients will be randomly assigned to either CBT-MS or treatment as usual (TAU). The stress management program will consist of 26 weekly group stress management training sessions followed by 12 monthly booster sessions to encourage maintenance of behavioral changes, Because MS exacerbation is episodic, with annual prevalence rates of .61 - 1.68, longer maintenance of behavioral changes will greatly increase the power to detect effects. Patients will be followed for 6 months following cessation of treatment and booster sessions. To encourage retention, TAU patients will be offered 26 weeks of CBT-MS after completing the study. Consistent with Phase II clinical trials in MS, the primary outcome will be Gd+ MRI brain lesions acquired at screening, and months 3, 6, 12, 18, and 24. Secondary neuroimaging outcomes will include T2-weighted MRI and brain parenchymal fraction (BPF). Secondary clinical outcomes will include MS exacerbation rate, progression of disability, and neuropsychological impairment. Quality of life will be examined as a secondary outcome to evaluate clinical utility. We also wilt enhance our understanding of mechanisms by examining potential psychosocial, immune, and endocrine mediators of the relationship betweenSLEs and clinical and neuroimaging markers of MS inflammation.